Poor Outcomes in a Cohort of HIV-Infected Adolescents Undergoing Treatment for Multidrug-Resistant Tuberculosis in Mumbai, India.

Poor Outcomes in a Cohort of HIV-Infected Adolescents
Undergoing Treatment for Multidrug-Resistant
Tuberculosis in Mumbai, India
Petros Isaakidis1
*, Roma Paryani1
, Samsuddin Khan1
, Homa Mansoor1
, Mamta Manglani2
,
Asmaa Valiyakath1
, Peter Saranchuk3
, Jennifer Furin4
1 Me´decins Sans Frontie`res, Mumbai, India, 2 Pediatric Centre of Excellence for HIV Care, Lokmanya Tilak Municipal Medical College and General Hospital, Sion, Mumbai,
India, 3 Southern Africa Medical Unit, Me´decins Sans Frontie`res, Cape Town, South Africa, 4 Tuberculosis Research Unit, Case Western Reserve University, Cleveland, Ohio,
United States of America
Abstract
Background: Little is known about the treatment of multidrug-resistant tuberculosis (MDR-TB) in HIV-co-infected
adolescents. This study aimed to present the intermediate outcomes of HIV-infected adolescents aged 10–19 years
receiving second-line anti-TB treatment in a Me´decins Sans Frontie`res (MSF) project in Mumbai, India.
Methods: A retrospective review of medical records of 11 adolescents enrolled between July 2007 and January 2013 was
undertaken. Patients were initiated on either empirical or individualized second-line ambulatory anti-TB treatment under
direct observation.
Results: The median age was 16 (IQR 14–18) years and 54% were female. Five (46%) adolescents had pulmonary TB (PTB),
two (18%) extrapulmonary disease (EPTB) and four (36%) had both. Median CD4 count at the time of MDR-TB diagnosis was
162.7 cells/ml (IQR: 84.8–250.5). By January 2013, eight patients had final and 3 had interim outcomes. Favourable results
were seen in four (36.5%) patients: one was cured and three were still on treatment with negative culture results. Seven
patients (64%) had poor outcomes: four (36.5%) died and three (27%) defaulted. Three of the patients who died never
started on antiretroviral and/or TB treatment and one died 16 days after treatment initiation. Two of the defaulted died soon
after default. All patients (100%) on-treatment experienced adverse events (AEs): two required permanent discontinuation
of the culprit drug and two were hospitalized due to AEs. No patient required permanent discontinuation of the entire
second-line TB or antiretroviral regimens.
Conclusions: Early mortality and mortality after default were the most common reasons for poor outcomes in this study.
Early mortality suggests the need for rapid diagnosis and prompt treatment initiation, and adolescents might benefit from
active contact-tracing and immediate referral. Default occurred at different times, suggesting the need for continuous,
intensified and individualized psychosocial support for co-infected adolescents. Operational research among co-infected
adolescents will be especially important in designing effective interventions for this vulnerable group.
Citation: Isaakidis P, Paryani R, Khan S, Mansoor H, Manglani M, et al. (2013) Poor Outcomes in a Cohort of HIV-Infected Adolescents Undergoing Treatment for
Multidrug-Resistant Tuberculosis in Mumbai, India. PLoS ONE 8(7): e68869. doi:10.1371/journal.pone.0068869
Editor: Robert J. Wilkinson, Institute of Infectious Diseases and Molecular Medicine, South Africa
Received March 21, 2013; Accepted June 1, 2013; Published July 19, 2013
Copyright: ß 2013 Isaakidis et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits
unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: No current external funding sources for this study.
Competing Interests: The authors have declared that no competing interests exist.
* E-mail: msfocb-asia-epidemio@brussels.msf.org
Introduction
Multidrug-resistant tuberculosis (MDR-TB)–defined as strains
of TB with in vitro resistance to at least isoniazid and rifampin–is a
major public health problem [1]. In 2010, it was estimated that
there were 650,000 prevalent MDR-TB cases, few of which were
actually diagnosed and treated. In fact, fewer than 40,000 patients
have been put on World Health Organization (WHO)-recom-
mended therapy in the last decade [2]. Inadequate diagnosis and
treatment of MDR-TB is even worse in children, who represent an
estimated 10–20% of all cases, up to 80,000 each year [3–4]. The
published literature reports only a small number of pediatric
patients receiving treatment, and a recent meta-analysis of
pediatric MDR-TB treatment outcomes included only 315
children [5].
What little pediatric data does exist tends to group all outcomes
together, despite the fact that the data represents children as young
as a few months old and others up to 18 years of age [6]. It is
widely acknowledged that younger children face more challenges
in terms of diagnosis and medication dosing [7] while older
children, especially those in what is known as the ‘‘adolescent’’ age
group (defined by the World Health Organization as those aged
10–19 years [8]), may face more challenges with adherence given
their developmental state [9]. The literature on chronic disease
management in adolescents has shown that this population has
special physical and psychological needs [10–12]. Adolescents
PLOS ONE | www.plosone.org 1 July 2013 | Volume 8 | Issue 7 | e68869

often experience spurts of growth that may lead to under-dosing
with their medication [13]. Certain diseases, including TB, may
also present more aggressively in this population [14–15]. Perhaps
more significantly, adolescence is defined as a period of emotional
and psychological upheaval that can affect relationships with
health care providers and caregivers and ultimately adherence to
medical regimens [16–17]. In addition, adolescence is a time
period during which children must transition into adult roles; there
may be increased time constraints due to school, work or family
responsibilities [18–20]. All of these issues can affect the health
outcomes of adolescent populations with chronic diseases, such as
MDR-TB.
To date, there are no published reports characterizing MDR-
TB treatment outcomes in the adolescent population. This paper
fills that gap by presenting data from a cohort of 11 adolescent
patients diagnosed with MDR-TB in Mumbai, India, all of whom
were co-infected with HIV. The cohort is relatively small, but is
being reported here because it demonstrates some concerning
findings in the adolescent population undergoing treatment for
MDR-TB. Targeted interventions to improve MDR-TB treatment
outcomes in adolescents are also discussed.
Methods
Study Design, Setting and Study Population
This is a retrospective review of the medical records of HIV-
infected adolescents aged 10–19 years with culture-confirmed or
suspected MDR-TB, undertaken as part of a larger study on
MDR-TB treatment outcomes in Mumbai, India [21]. All patients
were enrolled to receive treatment with second-line anti-TB
medications in a Me´decins Sans Frontie`res (MSF) clinic. Patients
were referred to the clinic by public antiretroviral treatment
centers (ART Centers), including the Regional Pediatric ART
Centre, L.T.M. Medical College, Sion, Mumbai, which serves as
one of the Centres Of Excellence in Pediatric HIV Care in India.
Patients were also referred to the clinic by a network of community
non-governmental organizations. Eleven (11) adolescents enrolled
in care between July 2007 and January 2013 are included in this
analysis.
Treatment Protocol and Follow-up
The ambulatory, community-based MDR-TB treatment pro-
gram has been described in detail in a previous publication [21].
Individualized treatment regimens are designed for each patient,
based on drug susceptibility testing (DST) and prior treatment
history. Standardized empiric treatment is given to patients who
require immediate initiation due to disease severity or for those in
whom a DST result is not available but in whom MDR-TB is
diagnosed based on clinical findings, past TB treatment history
and/or history of contact with a known or suspected MDR-TB
patient. The standardized regimen follows international recom-
mendations [22] and includes six drugs: pyrazinamide, capreo-
mycin, moxifloxacin, ethionamide, cycloserine and p-aminosa-
licylic acid (PAS) and is modified as necessary if DST results
become available. Blood test monitoring was done every month
and sputum smear and culture every month during the intensive
phase and every three months during the continuation phase.
Treatment is continued for a minimum total duration of 18–20
months, including a minimum of 6–8 months intensive phase that
includes an injectable agent. Antiretroviral therapy (ART) against
HIV includes two nucleoside/tide reverse transcriptase inhibitors
(NRTIs) and one non-nucleoside reverse transcriptase inhibitor
(NNRTI) in a first-line ART regimen, while patients in need of
second-line ART receive a protease inhibitor-based regimen along
with NRTIs that are likely to be effective, based on HIV resistance
testing results.
The adolescent patients were evaluated and followed by a
multidisciplinary team of doctors, nurses, a psychologist and a
social worker. They were clinically evaluated every two weeks
during the first month of treatment and once a month thereafter.
Home visits were conducted by the clinic team as necessary in
order to provide social and emotional support to the adolescents
and their families. At the community level, a network of public and
private health structures and non-governmental organizations
(NGOs) acted as providers of directly observed therapy (DOT) for
the MDR-TB medication. DOT providers were given training on
adverse events, adherence monitoring and pill counts, and referral
pathways for patients with poor adherence.
Data Collection and Analysis
Demographic and clinical information were systematically
recorded in clinical files and entered into an electronic database.
Information on HIV and antiretroviral therapy was collected in
the same patient file but entered in a separate database. Each
patient had a unique identification code that was used in both
databases. Possible outcomes, defined according to WHO
guidelines, included: cure, treatment completed, death, default,
transfer out, treatment failure, and ‘alive and on treatment’.
Ethics
This study has met the criteria for analysis of routinely collected
program data of the MSF Ethics Review Board, Geneva,
Switzerland. As this was a study of routinely collected monitoring
data, informed consent from the patients was not obtained. The
named ethics committee waived the need for consent.
Results
Eleven adolescents, aged 10 to 19 years, diagnosed with MDR-
TB and co-infected with HIV are reported here. All had
perinatally acquired HIV. The median age was 16 [Interquartile
Range (IQR): 14–18] and 54 percent were female. All except one
had a past history of TB treatment and four of them were contacts
of known drug-resistant TB patients. Five (46%) adolescents had
pulmonary TB, two (18%) had extrapulmonary disease and four
(36%) had both pulmonary and extrapulmonary TB (Table 1).
The median CD4 count at the time of MDR-TB diagnosis was
162.7 cells/ml (IQR: 84.8–250.5). Five patients were on ART at
the time of the MDR-TB diagnosis: two of them were on ART for
more than 2 years and three of them for six months or less.
Another three patients were started on ART following initiation of
DR-TB treatment: two patients after seven months and one
patient after one month of TB treatment (Table 2). The median
time from diagnosis of MDR-TB to initiation of second-line
treatment was 10 days (IQR: 7–12). Three patients did not start
antiretroviral and second-line TB treatments as they died soon
after enrolment (Figure 1). Routine HIV viral load monitoring was
not available during the early years of the program.
By January 2013, eight patients had final outcomes and three
had interim outcomes (Table 3). Favourable outcomes were seen
in 4 (36%) of the patients, one of whom was cured and three of
whom were still on treatment with negative smears and/or
cultures and improving clinical signs. Two of these latter patients
were about to complete their course of second-line anti-TB
treatment at the time of this analysis and they were doing very
well.
The remaining 7 patients (64%) had poor treatment outcomes:
four of these patients (36.5%) died and three of them (27%)
Outcomes in HIV/MDR-TB Co-Infected Adolescents

defaulted treatment. Of the four who died, three never started on
MDR-TB and ART treatments and one died 16 days after
treatment initiation. Treatment interruptions were recorded in all
three patients who defaulted treatment. Two of the adolescents
who defaulted died soon after they abandoned treatment at 3 and
17 months, reportedly due to adverse events and social problems
respectively. One patient, a 15 year-old female, defaulted three
weeks before treatment completion (at 21 months). The girl
declined both antiretroviral and anti-TB treatments despite an
excellent clinical response and lack of adverse events. We traced
the patient and identified a non-supportive, problematic family
environment (parental death, history of sexual abuse). Her elder
sister, also HIV/MDR-TB co-infected and part of this same
cohort, had died. The girl had a partner to whom she was initially
unwilling to disclose her status, but eventually did give her consent
for couple counseling.
Refusal to start treatment and treatment interruptions were
frequently (4/8) observed in this cohort of adolescents. An
example illustrating the complexity of treatment acceptance and
adherence is an orphan male patient who had started anti-TB
treatment but refused to start on antiretroviral treatment. He later
abandoned his anti-TB treatment only to restart 5 months later as
his condition had deteriorated. He is presently on both treatment
regimens. However the family is worried about TB transmission
and is trying to send him to a hospice. As a result, the patient is
experiencing behavioral issues due to a perceived fear of
abandonment. Constant supportive counseling has thus far
ensured that he stays on treatment, while additional family
counseling is being offered.
All eight patients (100%) who started on treatment experienced
adverse events (AE); 2 required permanent discontinuation of the
culprit drug and 2 patients had to be hospitalized due to AEs (both
for hypokalaemia). The most common adverse events were
gastrointestinal intolerance (5/8 patients) followed by peripheral
neuropathy (3/8) and psychiatric events (3/8). Adverse events and
the time of occurrence are shown in Table 4. None of the eight
patients has required permanent discontinuation of the entire
second-line anti-TB or antiretroviral regimen.
Discussion
This study shows poor treatment outcomes in a cohort of HIV-
infected adolescents being treated for MDR-TB. Compared with
their adult counterparts in a previous publication [23], these
adolescents have both higher rates of death and default. These
results are of concern and suggest the need for urgent interven-
tions.
The majority of the adolescents (6/11) in this cohort died, and
there may be several explanations for this. First, HIV co-infection
has been shown to be a risk factor for mortality among persons
with MDR-TB [24]. Co-infected patients may have severe forms
of Immune Reconstitution Inflammatory Syndrome (IRIS)
following ART initiation that can be associated with mortality
[25]. There may be drug-drug interactions between second-line
anti-TB medications and ART that could result in decreased
efficacy of therapy [26]. Second, extent of disease and drug
resistance, particularly to the fluoroquinolones, have also been
associated with worse treatment outcomes in other cohorts [27–
28] and may have played a role here, given that 75% of available
DST results showed resistance to this group of drugs.
While these factors may have played a role in the high mortality
seen in this study, it should be noted that four of the six patients
who died did so either prior to or within three weeks of initiating
therapy. Such ‘‘early deaths’’ have been described in other cohorts
and are usually considered ‘‘failure to treat’’ as opposed to
‘‘treatment failures’’ [29]. These deaths can generally be ascribed
to problems with timely diagnosis and referral rather than
ineffective treatment practices [30]. The high early mortality in
this cohort suggests that special strategies should be deployed to
diagnose and refer adolescents with suspected MDR-TB early in
the course of their disease [31]. Although adolescents may be able
to more easily provide sputum samples for diagnosis when
compared with children, they may be less likely to follow up on
referrals [32]. A potential strategy for earlier diagnosis is active
screening and immediate clinical referral of all household contacts
of persons with MDR-TB [33], given that more than one-third of
the adolescents in this study had a known MDR-TB contact; had
Table 1. Demographic and Clinical Characteristics of the Mumbai HIV/MDR-TB co-infected adolescent cohort, 2007–2013 (N = 11).
Characteristic n (%)
Age, median (IQR) years 16 (14–18)
Female gender 6 (54)
Site of disease
Pulmonary 5 (46)
Extrapulmonary 2 (18)
Pulmonary+Extrapulmonary 4 (36)
Previous TB treatment 10/11 (91)
MDR-TB Contact 4/11 (37)
Resistance (when DST available)
H 9/9 (100)
R 9/9 (100)
E 7/9 (78)
FQ 6/8 (75)
Injectable 1/8 (13)
CD4 count at time of MDR-TB diagnosis, cells/ml, median (IQR) 162.7 (84.8–250.5)
IQR: interquartile range; H: isoniazid; R: rifampicin; E: ethambutol; FQ: fluoroquinolones.
doi:10.1371/journal.pone.0068869.t001

Figure 1. Flowchart of the Mumbai HIV/MDR-TB co-infected adolescent cohort, 2007–2013.
doi:10.1371/journal.pone.0068869.g001

they been identified through an active case-finding strategy,
perhaps they would have been diagnosed more quickly and
benefitted from earlier treatment.
Discontinuation of therapy was also frequently reported in this
study, with three (37.5%) of eight adolescents starting both
antiretroviral and anti-TB therapy eventually defaulting. This is
compared with a general loss to follow-up rate in this HIV
programme of less than 3% [34]. HIV co-infection may have been
a factor in patient discontinuation of therapy due to increased pill
burden on ART or the occurrence of adverse events [35–37] that
may result from interactions between TB and HIV drugs, or
additive drug-related side effects. In addition to the complications
of HIV co-infection, this adolescent cohort has had other risk
factors for default from therapy, including family and social
problems, unwillingness to disclose their status, and discrimina-
tion.
The story of the adolescent patient who defaulted just a few
weeks before treatment completion clearly illustrates the complex-
ity of factors that influence the behavior of adolescents who are
HIV-infected and at the same time have to go through a long
course of an intolerable and toxic treatment regimen. We have
observed that patients that begin to feel better while on treatment
prefer to get back to their normal routine: these activities of daily
living then take priority over their health. All adolescents in this
Mumbai cohort attended school at some point; it is interesting to
mention that none of them has disclosed their status at school.
All patients on treatment in this adolescent cohort experienced
similar adherence issues: they all reported the high pill burden, the
side effects, and the long duration of the treatment as major
Table 2. Clinical Characteristics of the Mumbai HIV/MDR-TB co-infected adolescent cohort, 2007–2013.
Age/Sex CD4* ART Regimen ART Started TB Site Smear Culture Resistance DR Type 2nd
-Line TB Regimen
1 14/M 243 D4T+3TC+EFV 5 months prior P+EP (Abd LN) NEG POS S,H,R,E,Km,PAS,Ofx,Eto XDR Cm,Lfx,Eto,Cs,Amcl
2 10/M 273 D4T+3TC+NVP 7 months after P NEG POS S,H,R,E,Ofx,Eto Pre-XDR Km,Mfx,Eto,Cs,PAS,Z,Amcl
3 18/F 125 TDF+3TC+EFV 5 months prior P POS POS S,H,R,E,Ofx Pre-XDR Km,Mfx,Eto,Cs,PAS
4 13/F 147 No ART Never EP (LN) POS POS S,H,R,E,Ofx Pre-XDR
5 18/F No ART Never P POS POS S,H,R,E MDR
6 16/F 92 D4T+3TC+EFV 6 months prior P+EP (Cereb) POS POS S,H,R,E,PAS,Z MDR Cm,Mfx,Eto,PAS,Z,H,Amcl
7 15/F 199 AZT+3TC+NVP 7 months after P POS POS S,H,R,E,PAS,Z MDR Km,Mfx,Eto,Cs,Amcl,H,E
8 19/F 290 TDF+3TC+ATV/r 28 months prior P NEG POS S,H,R,E,Ofx,PAS Pre-XDR Cm,Mfx,Eto,Cs,H,Cfz,Z
9 14/M 159 ABC+3TC+LPV/r 71 months prior EP Abd NEG NEG _ Empirical Cm,Mfx,Eto,Cs,PAS,Z
10 16/M 36 No ART Never P+EP (Abd LN) NEG NEG _ Empirical
11 18/M 63 TDF+3TC+EFV 1 month after P+EP (Abd) NEG POS S,H,R,E,Ofx,PAS,Mfx,Z Pre-XDR Cm,Lfx,Eto,Cs,Amcl,Hh,Cfz
M: male; F: female; D4T: stavudine; 3TC: lamivudine; EFV: efavirenz; TDF: tenofovir; AZT: zidovudine; ABC: abacavir; NVP: nevirapine; ATV/r: atazanavir/ritonavir; LPV:
lopinavir; PTB: pulmonary tuberculosis; EPTB: extra-pulmonary tuberculosis; Abd; abdominal; Cereb; cerebral, LN: lymph node; NEG: negative; POS: positive; S:
streptomycin; Cm: capreomycin; Km: kanamycin; Lfx: levofloxacin; Eto: ethionamide; CS: cycloserine; Amcl: amoxicillin/clavulanic acid; Mfx: moxifloxacin; Ofx; ofloxacin;
PAS; para-aminosalicylic acid; Z: pyrazinamide; H: isoniazid; Hh: high dose isoniazid; E: ethambutol; Cfz: clofazimine; XDR: extensively drug-resistant; MDR: multidrug-
resistant.
*at time of MDR-TB diagnosis.
Table 3. Outcomes of the Mumbai HIV/MDR-TB co-infected adolescent cohort, 2007–2013.
NoAge/Sex MDR Tx Start Date Outcome Time on Treatment Reason for default/Cause of death/Comments
1 14/M 27.07.2007 Defaulted 17 Months Patient defaulted after 17 months of treatment and then died 1 month after
default. Convulsions, Brain Tuberculoma.
2 10/M 31.08.2007 Cured 18 Months
3 18/F 19.06.2008 Defaulted 3 Months Patient died 1.5 months after default. Reason for default: adverse events & social
issues. Cause of death not ascertained.
4 13/F Never Died 0 Months Died before treatment, 1 month after enrolment
5 18/F Never Died 0 Months Patient declined treatment and died 2 months later
6 16/F 15.02.2011 Died 16 Days Brain Tuberculoma
7 15/F 22.02.2011 Defaulted 21 Months Patient defaulted a few weeks before treatment completion due to social issues
(family deaths, sexual abuse) & personal issues (sexual debut, not willing to
disclose status to partner)
8 19/F 12.05.2011 Alive on Treatment 21 Months Patient has culture converted, about to complete treatment
9 14/M 24.11.2011 Alive on Treatment 15 Months Patient in excellent clinical condition
10 16/M Never Died 0 Months Died before treatment, 1 month after enrolment. Acute renal failure.
11 18/M 23.10.2012 Alive on Treatment 4 Months Adherence problems (behavioral issues, adverse events)

challenges in their daily life. As expected, patients with good
support and patients who experienced low to no discrimination
demonstrated better adherence. We have found that supportive
counseling is important not just for the patient but also for the
family. Education about treatment and adherence issues is
important for the family and the caretakers so that they
understand the need to support the patient through this difficult
treatment. On the other hand, adolescents expressed that ‘‘the
constant nagging of the caretaker’’ worked against their adher-
ence. Despite the degree of support and the exposure to stigma
and discrimination, all adolescents were conscious of how
conspicuous they were during their daily visit to DOT centers,
so much so that some preferred to avoid going to the DOT centers
at the expense of their health. Adolescents want to experience
‘‘normal’’ lives and ‘‘pretended to be normal’’ rather than ‘‘taking
the steps to a better health’’ (patients quotes recorded during
routine counseling sessions).
Adverse events were frequent in this cohort and psychiatric
events were worryingly common. We have recently introduced a
baseline mental health evaluation in order to screen for depression
and other mental health issues. We have also found that aggressive
management of adverse events is necessary to ensure short and
long term adherence.
This study has a number of limitations, most of which are
related to the small sample size. Clearly, there is a need to evaluate
adolescents undergoing treatment for MDR-TB on a larger scale.
Second, all of the patients were infected with HIV and thus the
results are not likely generalizable to HIV-negative adolescents
with MDR-TB. Finally, this was a retrospective review of medical
records that is subject to all the biases inherent with such
methodology. In spite of these limitations, the trends identified in
this small cohort are of sufficient concern to be reported to the
scientific community so that increased attention can be given to
adolescent populations with MDR-TB.
Conclusion
Treatment outcomes seen in HIV-infected adolescents receiving
community-based MDR-TB treatment in Mumbai, India were
overwhelming poor, with a majority of patients either dying or
defaulting from therapy. While some of this may have been due to
the complicated treatment regimens required for people with HIV
and MDR-TB in general, the data suggest the need for targeted
interventions focused on adolescents. Active case-finding, espe-
cially among younger contacts of DR-TB cases, and shepherded
referrals into treatment could decrease mortality from the disease.
Targeted adherence counseling and social support around life
events that are common in adolescence could also be a strategy for
reducing discontinuation of therapy. Excellent treatment outcomes
should be possible for adolescents suffering from MDR-TB, given
the encouraging treatment results seen in both pediatric and adult
cohorts with the disease. Operational research looking at
interventions to improve outcomes in adolescents is sorely needed.
Strategies that account for the unique needs of this population
should be developed and adapted to ensure a safe and healthy
transition into adulthood.
Table 4. Treatment-related adverse events in the Mumbai HIV/MDR-TB co-infected adolescent cohort, 2007–2013.
Age/Sex 2ND
line TB Regimen ART Regimen Adverse events (AEs) Grade
Possible culprit
drug Time (weeks)
1 14/M Cm,Lfx,Eto,Cs,Amcl D4T+3TC+EFV Convulsions severe Cs 5
GI Intolerance mild Eto 9
Peripheral Neuropathy mild D4T, Cs 56
2 10/M Km,Mfx,Eto,Cs,PAS,Z,Amcl D4T+3TC+NVP Hearing Loss mild Km 4
3 18/F Km,Mfx,Eto,Cs,PAS TDF+3TC+EFV (previously
on d4T)
Peripheral Neuropathy moderate D4T 4
4 13/F No TB Treatment No ART
5 18/F No TB Treatment No ART
6 16/F Cs,Mfx,Eto,PAS,Z,H,Amcl D4T+3TC+EFV GI Intolerance mild Eto, PAS 1
Psychiatric (Psychosis) severe Cs, EFV 2
7 15/F Km,Mfx,Eto,Cs,Amcl,H,E AZT+3TC+NVP GI Intolerance moderate Eto, Amcl 2
Anxiety Disorder mild Cs 2
8 19/F Cm,Mfx,Eto,Cs,H,Cfz,Z TDF+3TC+ATV/r Nephrotoxicity mild Cm, TDF 4
Psychiatric (Psychosis) severe Cs 20
9 14/M Cm,Mfx,Eto,Cs,PAS,Z ABC+3TC+LPV/r GI Intolerance moderate Eto, PAS 4
Hypothyroidism mild Eto, PAS 12
Hypokalemia mild Cm 40
10 16/M No TB Treatment No ART
11 18/M Cm,Lfx,Eto,Cs,Amcl,Hh,Cfz TDF+3TC+EFV GI Intolerance mild Eto, Amcl 1
Hypokalemia moderate Cm 4
Peripheral Neuropathy mild Cs, Eto 9
Hypothyroidism mild Eto 11
M: male; F: female; S: streptomycin; Cm: capreomycin; Km: kanamycin; Lfx: levofloxacin; Eto: ethionamide; CS: cycloserine; Amcl: amoxicillin/clavulanic acid; Mfx:
moxifloxacin; PAS: para-aminosalicylic acid; Z: pyrazinamide; H: isoniazid; Hh: high dose isoniazid; E; ethambutol, Cfz: clofazimine; GI: gastrointestinal; CrCl: creatinine
clearanc.

Acknowledgments
The authors wish to acknowledge the contribution of health care workers
from the MSF project, staff from the LTMG Hospital, Sion, as well as the
teenagers suffering from HIV and MDR-TB and their families. We are
grateful to Tony Reid for his support with the ethics clearance and his
editorial support.
Author Contributions
Conceived and designed the experiments: PI. Performed the experiments:
SK HM AV RP. Analyzed the data: PI SK RP. Contributed reagents/
materials/analysis tools: MM PS JF. Wrote the paper: PI JF SK.
References
1. World Health Organization (2008) Anti-tuberculosis drug resistance in the world
Report no. 4. Geneva, Switzerland. ISBN 978 92 4 156361 1. WHO/HTM/
TB/2008.394.
2. World Health Organization (2011) Towards universal access to diagnosis and
treatment of multidrug-resistant and extensively drug-resistant tuberculosis by
2015 Geneva, Switzerland. ISBN: 978 92 4 150133. WHO/HTM/TB/2011.3.
3. Seddon JA, Hesseling A, Willemse M, Donald PR, Schaaf HS (2011) Culture-
Confirmed Multidrug-Resistant Tuberculosis in Children: Clinical Features,
Treatment, and Outcomes. Clin Infect Dis. doi: 10.1093/cid/cir772.
4. Schaaf HS (2007) Drug-resistant tuberculosis in children. S Afr Med J: 97: 995–
97.
5. Ettehad D, Schaaf HS, Seddon JA, Cooke GS, Ford N (2012) Treatment
outcomes for children with multidrug-resistant tuberculosis: a systematic review
and meta-analysis. The Lancet Infectious Diseases. 12(6): 449–56.
6. Drobac PC, Mukherjee JS, Joseph JK, Mitnick C, Furin JJ, et al. (2006)
Community-based therapy for children with multidrug-resistant tuberculosis.
Pediatrics. 117(6): 2022–9.
7. Coelho Filho JC, Caribe MA, Caldas SC, Martins Netto E (2011) Is tuberculosis
difficult to diagnose in childhood and adolescence?. Jornal Brasileiro De
Pneumologia: Publicacao Oficial Da Sociedade Brasileira De Pneumologia E
Tisilogia. 37(3): 288–93.
8. World Health Organization (2013) Adolescent Health. http://www.who.int/
topics/adolescent_health/en/. Accessed February 12, 2013.
9. Perez-Velez CM (2012) Pediatric tuberculosis: new guidelines and recommen-
dations. Curr Opin Pediatr. Jun;24(3): 319–28.
10. Geldenhuys H, Sorsdahl K, Kafaar F, Hatherill M, Hanekom WA, Stein DJ, et
al. (2011) Risky behaviour and psychosocial correlates in adolescents - is there a
link with tuberculosis?. African Journal of Psychiatry. 14(5): 383–7.
11. Greenley RN, Kunz JH, Biank V, Martinez A, Miranda A, et al. (2012)
Identifying youth nonadherence in clinical settings: data-based recommenda-
tions for children and adolescents with inflammatory bowel disease. Inflamma-
tory Bowel Diseases. 18(7): 1254–9.
12. Nichols SL, Montepiedra G, Farley JJ, Sirois PA, Malee K, et al. (2012) PACTG
P1042S Team. Cognitive, academic, and behavioral correlates of medication
adherence in children and adolescents with perinatally acquired HIV infection.
Journal of Developmental & Behavioral Pediatrics. 33(4): 298–308.
13. Chiang CY, Bai KJ, Lee CN, Enarson DA, Suo J, et al. (2010) Inconsistent
dosing of anti-tuberculosis drugs in Taipei, Taiwan.International Journal of
Tuberculosis & Lung Disease. 14(7): 878–83.
14. Thampi N, Stephens D, Rea E, Kitai I (2012) Unexplained deterioration during
antituberculous therapy in children and adolescents: clinical presentation and
risk factors. Pediatric Infectious Disease Journal. 31(2): 129–33.
15. Phongsamart W, Kitai I, Gardam M, Wang J, Khan K (2009) A population-
based study of tuberculosis in children and adolescents in Ontario. Pediatric
Infectious Disease Journal. 28(5): 416–9.
16. M’imunya JM, Kredo T, Volmink J (2012) Patient education and counselling for
promoting adherence to treatment for tuberculosis. Cochrane Database of
Systematic Reviews. 5: CD006591.
17. Chandwani S, Koenig LJ, Sill AM, Abramowitz S, Conner LC, et al. (2012)
Predictors of antiretroviral medication adherence among a diverse cohort of
adolescents with HIV. Journal of Adolescent Health. 51(3): 242–51.
18. Arnone J, Fitzsimons V (2012) Adolescents with celiac disease: a literature review
of the impact developmental tasks have on adherence with a gluten-free diet.
Gastroenterology Nursing. 35(4): 248–54.
19. Hodgson I, Ross J, Haamujompa C, Gitau-Mburu D (2012) Living as an
adolescent with HIV in Zambia – lived experiences, sexual health and
reproductive needs. AIDS Care. 24(10): 1204–10.
20. Fair CD, Sullivan K, Dizney R, Stackpole A (2012) ‘‘It’s like losing a part of my
family’’: transition expectations of adolescents living with perinatally acquired
HIV and their guardians. AIDS Patient Care & Stds. 26(7): 423–9.
21. Isaakidis P, Cox HS, Varghese B, Montaldo C, Da Silva E, et al. (2011)
Ambulatory multi-drug resistant tuberculosis treatment outcomes in a cohort of
HIV-infected patients in a slum setting in Mumbai, India. PLoS ONE
[Electronic Resource]. 6(12): e28066.
22. Mukherjee JS, Rich ML, Socci AR, Joseph JK, Viru FA, et al. (2004)
Programmes and principles in treatment of multidrug-resistant tuberculosis.
Lancet. 363(9407): 474–81, 2004.
23. Isaakidis P, Varghese B, Mansoor H, Cox HS, Ladomirska J, et al. (2012)
Adverse events among HIV/MDR-TB co-infected patients receiving antiretro-
viral and second line anti-TB treatment in Mumbai, India.PLoS ONE
[Electronic Resource]. 7(7): e40781, 2012.
24. Gandhi NR, Shah NS, Andrews JR, Vella V, Moll AP, et al. (2010) Tugela Ferry
Care and Research (TF CARES) Collaboration. HIV coinfection in multidrug-
and extensively drug-resistant tuberculosis results in high early mortality.
American Journal of Respiratory & Critical Care Medicine. 181(1): 80–6.
25. Naidoo K, Yende-Zuma N, Padayatchi N, Naidoo K, Jithoo N, et al. (2012) The
immune reconstitution inflammatory syndrome after antiretroviral therapy
initiation in patients with tuberculosis: findings from the SAPiT trial. Annals of
Internal Medicine. 157(5): 313–24.
26. Furin JJ, Johnson JL (2005) Recent advances in the diagnosis and management
of tuberculosis. Current Opinion in Pulmonary Medicine. 11(3): 189–94.
27. Mitnick CD, Shin SS, Seung KJ, Rich ML, Atwood SS, et al. (2008)
Comprehensive treatment of extensively drug-resistant tuberculosis. New-
EnglandJournalofMedicine. 359(6): 563–74.
28. Chan ED, Strand MJ, Iseman MD (2008) Treatment outcomes in extensively
resistant tuberculosis. New England Journal of Medicine. 359(6): 657–9.
29. Mitnick C, Bayona J, Palacios E, Shin S, Furin J, et al. (2003) Community-based
therapy for multidrug-resistant tuberculosis in Lima, Peru. New England Journal
of Medicine. 348(2): 119–28.
30. Farmer P (1999) Managerial successes, clinical failures. International Journal of
Tuberculosis & Lung Disease. 3(5): 365–7.
31. Sachdeva KS, Kumar A, Dewan P, Kumar A, Satyanarayana S (2012) New
vision for Revised National Tuberculosis Control Programme (RNTCP):
Universal access – ‘‘reaching the un-reached’’. Indian Journal of Medical
Research. 135(5): 690–4.
32. Fairlie L, Beylis NC, Reubenson G, Moore DP, Madhi SA (2011) High
prevalence of childhood multi-drug resistant tuberculosis in Johannesburg,
South Africa: a cross sectional study. BMC Infectious Diseases. 11: 28.
33. Singla N, Singla R, Jain G, Habib L, Behera D (2011) Tuberculosis among
household contacts of multidrug-resistant tuberculosis patients in Delhi, India.
International Journal of Tuberculosis & Lung Disease. 15(10): 1326–30.
34. Errol L, Isaakidis P, Zachariah R, Ali M, Pilankar G, et al. (2012) Tracing
patients on antiretroviral treatment lost-to-follow-up in an urban slum in India.
J Adv Nurs 68(11): 2399–409.
35. Nansera D, Bajunirwe F, Elyanu P, Asiimwe C, Amanyire G, Graziano FM
(2012) Mortality and loss to follow-up among tuberculosis and HIV co-infected
patients in rural southwestern Uganda. International Journal of Tuberculosis &
Lung Disease. 16(10): 1371–6.
36. Garrido Mda S, Penna ML, Perez-Porcuna TM, de Souza AB, Marreiro Lda S,
et al. (2012) Factors associated with tuberculosis treatment default in an endemic
area of the Brazilian Amazon: a case control-study.PLoS ONE [Electronic
Resource]. 7(6): e39134.
37. Maruza M, Albuquerque MF, Coimbra I, Moura LV, Montarroyos UR, et al.
(2011) Risk factors for default from tuberculosis treatment in HIV-infected
individuals in the state of Pernambuco, Brazil: a prospective cohort study.BMC
Infectious Diseases. 11: 351.

Poor Outcomes in a Cohort of HIV-Infected Adolescents Undergoing Treatment for Multidrug-Resistant Tuberculosis in Mumbai, India.

Recomendados

Recomendados

Mais conteúdo relacionado

Mais procurados

Mais procurados (20)

Semelhante a Poor Outcomes in a Cohort of HIV-Infected Adolescents Undergoing Treatment for Multidrug-Resistant Tuberculosis in Mumbai, India.

Semelhante a Poor Outcomes in a Cohort of HIV-Infected Adolescents Undergoing Treatment for Multidrug-Resistant Tuberculosis in Mumbai, India. (20)

Último

Último (20)

Poor Outcomes in a Cohort of HIV-Infected Adolescents Undergoing Treatment for Multidrug-Resistant Tuberculosis in Mumbai, India.